We propose to investigate the physiologic and morphologic changes induced by ultrasound in the developing heart. Although diagnostic ultrasound has many benefits, its use is not clearly free of risk to the developing fetus. The embryonic heart is often the target for ultrasound study to: determine heart rate, identify arrhythmias, evaluate pericardial effusion, rule out structural anomalies of the heart, and to evaluate and treat fetal distress. We have recently found that high intensity ultrasound can induce direct myocardial cell injury in the developing heart. In the mature heart, others have noted differing effects at different intensities with the possibility of enhanced performance at high intensities. Accordingly, we plan to study acute exposure to ultrasound for 5 or 30 minutes at four intensities ranging from 50 mW/cm2 to 1500 mW/cm2 in the embryonic chick heart to determine a "dose-response" curve Embryos at a critical stage of form-function development (Hamburger-Hamilton stage 18) will be evaluated by direct examination of cardiac function by cinephotoanalysis and of associated morphologic change by electron microscopy. Since the fetus is commonly studied by ultrasound when a disease state or altered physiologic condition is suspected, we further propose to examine the effect of ultrasound on the embryonic heart subjected to hypoxic stress. Hypoxia is commonly associated with times of fetal distress, and it may act by synergistic effects to allow embryonic injury at relatively low ultrasound intensity. Recent work shows that embryonic cardiac myocytes can be spared injury (e.g. hypoxia), or be allowed to repair, by providing a hypothermic environment. In the mature heart, some investigators have noted that ultrasound itself, at high intensity, may improve cardiac function by altering calcium movement. Accordingly, we plan to examine systematically the effects of ultrasound, ultrasound plus hypoxia, ultrasound plus hypothermia, and ultrasound plus intra-embryonic verapamil (calcium channel blocker). We expect to show that ultrasound, at certain levels, causes morphologic injury while, at other levels, alters myocardial function. Such responses can be modulated by changes in ambient oxygen, temperature, orcalcium flux within the heart. By examining embryos 24 hours after ultrasound exposure, we will study the possibility of repair. Conversely, ongoing injury in the form of a cardiac anomaly can be documented. The proposed research in our animal model will help to clarify mechanisms of myocardial damage induced by ultrasound and to possibly identify a way to protect the embryonic heart from injury.